Fusokines involving cytokines with strongly reduced receptor binding affinities

Abstract

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

The invention claimed is: 
     
       1. A composition comprising a fusion protein comprising at least two cytokines, wherein the cytokines are CC chemokine 20 (CCL20) and mutant human interleukin-1 beta (IL-1β) and wherein IL-1β comprises a mutation selected from R120G, Q131G, H146A, and Q148G that reduces binding activity of IL-1β to its receptor as compared to wild type IL-1β, and the CCL20 is wild-type and provides cell-specific targeting that restores activity of the mutant IL-1β on the targeted cells. 
     
     
       2. The composition of  claim 1 , further comprising a GGS linker. 
     
     
       3. The composition of  claim 1 , wherein the human IL-1β mutation is Q148G. 
     
     
       4. The composition of  claim 1 , wherein the human IL-1β mutation is R120G. 
     
     
       5. The composition of  claim 1 , wherein the human IL-1β mutation is Q131G. 
     
     
       6. The composition of  claim 1 , wherein the human IL-1β mutation is H146A.